This study aimed to evaluate the effects of Peste des petits ruminants (PPR) vaccine on cytokine and antibody levels in sheep when administered alone or in combination with Corynebacterium cutis lysate (CCL). The PPR vaccine group received a single subcutaneous axillary injection of the PPR vaccine (1 mL containing tissue culture infectious dose (TCID)50 attenuated live PPRV, n = 6) and the combination treatment (1 mL CCL and 1 mL PPR vaccine, n = 6) groups received a single subcutaneous axillary injection of both CCL and PPR vaccine. Blood samples were collected from sheep before the treatment and at different points after treatment (1, 3, 7, 14, 21, and 28 days). Plasma and serum samples were evaluated for antibody percentage, levels of cytokines IL-6, IL-10, IFN-γ, IL-4, IL-12, and IL-18, oxidative stress marker Thiobarbituric acid reactive substances, and hematological and biochemical parameters. Maximum protective antibody levels reach 3-4 weeks after vaccine administration. The combination treatment resulted in significant changes in IFN-γ, IL-4, IL-12, and IL-18 cytokine levels. These changes were not evident when only the PPR vaccine was administered and antibody percentage against PPRV was short term in PPR vaccine group. In conclusion, combined usage of the PPR vaccine with CCL resulted in a heightened cytokine response, leading to improved antibody level against PPR virus. Repeated CCL treatments can lead to earlier vaccine potency, provide protective efficacy for a longer time, and increase passive immunity.